2,5,7,10-tetraoxaundecane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2008-08-25 to 2008-12-10

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,5,7,10-tetraoxaudecane

IUPAC Name:

2,5,7,10-tetraoxaudecane

Details on test material:

- Name of test material (as cited in study report): 2,5,7,10-tetraoxaudecane (TOU)
- Physical state: liquid
- Analytical purity: 99.632%
- Impurities (identity and concentrations): water (0.142%); aldehydes (not found); alcohols (0.064%)
- Lot/batch No.: 0804061200
- Expiration date of the lot/batch: 06/04/2011
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: OFA

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Rivers Laboratories (Wilmington, MA)
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 180-250g
- Fasting period before study: Animals were fasted overnight prior to the test item administration and food returned at 4h post dose. Water was available ad libitum with no restriction.
- Housing: The rats were housed multiply in cages (group-caged per dose) in the animal facilities of CER-DHA.
- Diet : ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days in the experimental unit before use in the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 ± 5.5
- Humidity (%): 45-90
- Air changes (per hr): 10-30
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- For steps 1 and 2 of the procedure (administration of the test item at a final dose of about 300 mg/kg bw), the administrated solution was prepared by dissolving 10x the test item in corn oil in order to obtain an adequate administration volume. The administrated solution was prepared in the hour preceding administration to animals and stored at room temperature.
- For steps 3 and 4 (administration of the test item at a final dose of about 2000 mg/kg bw), the test item was directly administrated to animals without dissolution in any vehicle.
- Lot/batch no. (if required): 117K0127


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: since no information about toxicity of the test item was available, the chosen starting dose level was 300 mg/kg bw as recommended by OECD guideline for animal welfare.

Doses:

Steps 1 and 2 of the procedure: administration of the test item at a final dose of about 300 mg/kg bw
Steps 3 and 4: administration of the test item at a final dose of about 2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: At least once during the first 30 minutes, periodically during the first 24h, with special attention given during the first 4 hours, and daily thereafter, for a total of 14 days.
- Frequency of weigthings: at the beginning of the test
- Necropsy of survivors performed: yes
- Other examinations performed: For animals surviving 24 hours or more, a microscopic examination of organs showing evidence of gross pathology was also considered.

Statistics:

None

Results and discussion

Preliminary study:

Not relevant

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According to the experimental scheme recommended by the OECD guideline 423, the test item can be classified in the category 5 of the GHS acute toxicity scheme which corresponds to a limit LD50 higher than 5000 mg/kg bw.

Mortality:

Step 1: 0/3
Step 2: 0/3
Step 3: 0/3
Step 4: 0/3

Clinical signs:

other: None

Gross pathology:

None

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

From these experiments and on the basis of the followed experimental scheme recommended by OECD TG 423, it can be concluded that TOU can be classified in the category 5 of the GHS acute toxicity scheme which corresponds to a limit LD50 higher to 5000 mg/kg bw for this test item.

Executive summary:

The objective of this study was to investigate the acute toxicity of the chemical compound 2,5,7,10 -tetraoxaudecane (TOU). In order to assess the toxicity of TOU, the method of predefined doses (acute toxic class method) was chosen. Ultimately, the method allows the tested substance to be ranked and classified according to the Globally Harmonised System (GHS) for the classification of chemicals which cause acute toxicity.

The acute toxic class method is a stepwise procedure based on biometric evaluations with fixed doses, adequately separated to enable a substance to be ranked for classification purposes and hazard assessment.

As recommended by the OECD TG 423, in a first step, TOU (mixed with corn oil) was administrated at a final dose level of about 300 mg/kg bw. Following administration, animals were regularly inspected for tolerance to the tested chemical compound administration. From the TOU administration time (T) to the exposure time T+4h, 9 to 10 observations were performed and recorded for each animal. The next observations, from D+2 (day ensuing the administration day D+1) to D+14 were performed daily with a frequency of 1 inspection point per day. After an observation period of 14 days, all 3 animals were alive without evident toxicological effect apparitions resulting from administration of TOU. Finally, animals were humanely killed by 1ml IP injection and macroscopically autopsied. All tissues were examined with a specific attention to hearth, liver, kidney, lungs, spleen, brain and stomach. As a result, no obvious pathological tissue alterations resulting from TOU oral administration were observed. Nevertheless, some lesions (especially pulmonary and hepathic congestion) probably caused by Nembutal anaesthesia. Indeed it is known that barbiturate induce in particular respiratory depression and are metabolised by the liver. Finally, all take in organs were individually identified and stored in formaldehyde solutions for further histological analyses if necessary.

In a second step, the initial administrated dose (about 300 mg/kg) was once again orally injected to 3 other female rats in order to confirm the results obtained in the first step. From the TOU administration time (T) to the exposure time T+4h, 10 observations were performed and recorded for each animal. The next observations, from D+2 (day ensuing the administration day D+1) to D+14 were performed daily with a frequency of one inspection point per day. From this second injection, after an observation period of 14 days, the same observations on those highlighted for the step 1, namely, no mortality in the test animal group and no evident external and internal pathological alterations resulting from administration of a TOU solution were highlighted. After anaesthesia (1ml Nembutal), rats were autopsied and sampled tissues (hearth, liver, kidneys, lungs, brain and stomach) were examined.

Results of the second step led to the following conclusion: administration of a TOU solution at a final dose volume of 300 mg/kg bw induces no acute toxicity in female rats.

Since no death and no toxicological effects were observed after a 300 mg/kg administration, TOU was administrated at a higher dose to 3 other female rats. TOU was administrated at a final oral dose of 2000 mg/kg bw as recommended by OECD TG 423. As for the steps 1 and 2, following oral administration, animals were carefully observed (6 observations for day D+1 and daily thereafter) for any toxicological adverse effects as described previously. Like for administration of TOU at 200 mg/kg bw, no death or toxicological adverse effect apparitions which could result from the TOU exposure were highlighted for a 14 days period following a first administration of TOU at 2000 mg/kg bw. Autopsies revealed no obvious pathological tissue alterations,except those probably caused by Nembutal, were highlighted for all tested animals. Sampled tissues (hearth, liver, kidneys, lungs, spleen, brain and stomach) were also conserved in appropriate media.

Repetition of the same exposure conditions (about 2000 mg/kg bw) to 3 other female rats and same observation period led to the same final observations and conclusions to that described for the first administration of a dose level at about 2000 mg/kg bw.

From these experiments and on the basis of the followed experimental scheme recommended by OECD TG 423, it can be concluded that TOU can be classified in the category 5 of the GHS acute toxicity scheme which corresponds to a limit LD50 higher to 5000 mg/kg bw for this test item.